The objective of the proposed research program is to develop and use a genetic system to examine the control of plasma membrane biogenesis in normal and malignant cells. The general approach to be followed is the use of lactoperoxidase catalyzed iodination and NaBH4 reduction of oxidized sugar residues to identify externally disposed membrane proteins and glycoproteins on normal cells isolated from inbred mice and on mouse tumor cells. Membrane proteins oriented toward the inside of these cells will be identified by lactoperoxidase catalyzed iodination of inside-out membrane on phagocytosed latex beads. The labeled membrane proteins will be separated on the basis of their charge and size. Inbred mouse strains will be screened for variation both quantitative and qualitative among the membrane proteins. Classical genetic and somatic genetic approaches would be used to establish a genetic basis for the variation. We are particularly interested in identifying quantitative variants of the polypeptides specified by the D and K regions of the H-2 complex. These variants would be used to both dissect the pathway of biogenesis of surface polypeptides and to study the regulation of membrane biogenesis.